Tuesday, 14 February 2012

Success rates for cornea transplants could be greatly improved following a major advance in genetically modifying donor corneas. Scientists at National University of Ireland Galway’s Regenerative Medicine Institute (REMEDI) have determined a method, in pre-clinical trials, to genetically modify donor corneas so that they are less likely to be rejected by the host immune system.

With more than 100,000 procedures a year worldwide, cornea transplantation (keratoplasty) is the most frequent transplant procedure. The cornea is the transparent, dome-shaped surface of the eye, and accounts for a large part of its focussing power. Transplantations can restore vision, reduce pain and improve the appearance of a damaged or diseased cornea.

Although keratoplasty is a procedure with good success rates, incidence of graft rejection still exists. For some high-risk patients, rejection rates can be as high as 50%. Using their breakthrough technique on the donor corneal tissue before grafting, the REMEDI team showed success in laboratory trials of decreased inflammatory response and protection against rejection.

The research team at NUI Galway, funded by Science Foundation Ireland, was led by Dr Thomas Ritter: “What we have succeeded in doing with the latest molecular biology techniques is to successfully encourage the donor cornea to produce ample PD-L1. It is known that Programmed Death-Ligand 1 (PD-L1) stops the activity of the body’s fighter immune cells and prohibits their ability to disrupt the transplantation process. By encouraging the donor cornea to produce PD-L1, it increased what known as the ‘immune privilege’ or ability of the eye to accept the graft.”

Dr Ritter added: “Potentially, what is most exciting is that these strategies could be of value for other transplant models. It could be applied, for example, to protect pancreatic islet cells transplanted for the treatment of type 1 diabetes.”

With Dr Ritter’s research, significant prolongation of transplant survival was observed which was associated with a reduction of the inflammatory response. No additional anti-rejection treatment was necessary for the recipients of the engineered corneas. These encouraging results may lead to a novel treatment protocol for ‘high-risk’ corneal graft recipients who are more likely to reject the graft than other patients. The research is published in this month’s American Journal of Transplantation.

Mr Gerry Fahy, Consultant Ophthalmologist at University Hospital Galway, who was involved in this study, commented on the results of this study: “Prevention of corneal transplant rejection is very important. This research describes a new exciting method of achieving that goal. I look forward to its translation into clinical use.”

Further investigations using mesenchymal stem cells by scientists at REMEDI will examine how these potent cells could also be used to prevent graft rejection.